Cancer immunotherapy using a DNA vaccine encoding the translocation domain of a bacterial toxin linked to a tumor antigen

C. F. Hung, W. F. Cheng, K. F. Hsu, C. Y. Chai, L. He, M. Ling, T. C. Wu

Research output: Contribution to journalArticlepeer-review

142 Citations (Scopus)

Abstract

Certain domains of bacterial toxins have been shown to facilitate translocation from extracellular and vesicular compartments into the cytoplasm. This feature represents an opportunity to enhance class I presentation of exogenous antigen to CD8+ T cells. We investigated this notion by creating a novel fusion of the translocation domain (domain II) of Pseudomonas aeruginosa exotoxin A (ETA(dII)) with a model tumor antigen, human papillomavirus type 16 E7, in the context of a DNA vaccine. Our in vitro studies indicated that cells transfected with ETA-(dII)/E7 DNA or dendritic cells pulsed with lysates containing ETA-(dII)/E7 protein exhibited enhanced MHC class I presentation of E7 antigen. Vaccination of mice with ETA(dII)/E7 DNA generated a dramatic increase in the number of ET-specific CD8+ T cell precursors (∼30-fold compared with wild-type E7 DNA) and converted a less effective DNA vaccine into one with significant potency against human papillomavirus type 16 E7-expressing murine tumors via a CD8-dependent pathway. These results indicate that fusion of the translocation domain of a bacterial toxin to an antigen may greatly enhance vaccine potency.

Original languageEnglish
Pages (from-to)3698-3703
Number of pages6
JournalCancer Research
Volume61
Issue number9
Publication statusPublished - 2001 May 1

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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